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Pharmaceutical Substances Syntheses, Patents, Applications - Part 22 potx

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CS Panoxyl Stiefel I: GB: Acnezide Galderma Acnidazil Janssen-Ci1ag- comb.. Nericur Schenng Panoxyl Stiefel Quinoderm Quinoderm- comb.. Benzomix Savoma Fatroxid Fatro Reloxyl Rdc USA: B

Trang 1

Bcnzphetamine B 21 1

F : Cutacnyl (Galderma)

Eclaran (Pierre Fabre)

EffacnC (Roche-Posay)

Pannogel (Labs CS)

Panoxyl (Stiefel) I:

GB: Acnezide (Galderma)

Acnidazil (Janssen-Ci1ag)-

comb

Benzamycin (Biog1an)-

comb

Nericur (Schenng)

Panoxyl (Stiefel)

Quinoderm (Quinoderm)- comb

Quinoped (Quinoderm)- comb

Acnidazil (Fisons ' 1talchimici)-comb

Benoxid (Brocades) Benzac (Galderma) Benioil Peros (Formulario Naz.)

Benzomix (Savoma) Fatroxid (Fatro) Reloxyl (Rdc)

USA: Benzac (Galderma) Benzagel (Dermik) Benzamycin (Dermik) Bcnzashave (Medicis) Brevoxyl (Stiefel) Desquam-E (Westwood- Squibb)

Desquam-X (Westwood- Squibb)

PanOxyl (S tiefel) Triaz (Medicis) Vanoxide-HC (Dermik)

RN: 156-08-1 MF: C,,H,,N MW: 239.36

LDSO: 227 mglkg (M, p.0.);

160 mglkg (R, p.0.)

CN: (+)-N,a-dimethyl-N-(phenylmethyl)benzeneethanamine

hydrochloride

RN: 541 1-22-3 MF: C,,H,,N HCI MW: 275.82 EINECS: 226-489-2

Reference(s):

US 2 789 138 (Upjohn; 1957; prior 1952)

(+)-deaxyephedrine benzyl chloride

Formulation(s): tabl 25 mg, 50 mg

Benzphetarnine

Trade Name(s):

F : Inapelyl (Upjohn); wfm GB: Didrex (Upjohn); wfm

Use: anti-emelic, tranquilizer RN: 63-12-7 MF: C22H32N20S MW: 404.51

CN: 2-(acety1oxy)-N,N-diethyl- 1,3,4,6,7, I1 b-hexahydro-9,1O-dimcthoxy-2H-benzo[n]quinolizine-3-

carboxamide

2-(3,4-dimethoxy- diethyl rnalonote ethyl N-(3,4-dimethoxy-

Trang 2

212 B Benzquinamide

ethyl 3.4-dihydro-6.7-di-

methaxy-1 -isoquinoline-

acetate

ethyl 1,2.3,4-tetrahydro- 6,7-dirnethoxy-1- isoquinolineocetate (11)

ethyl ocrylate ethyl 1-ethoxycorbonylrnethyl-

1,2,3.4-tetrahydro-6,7-dimethoxy-

ethyl 1.3.4.6.7.1 1 b-hexohydm- N.N-diethyl-1.3.4.6.7,ll b-hexahydro-9.10

dimethoxy-2-0x0-2H- 9,lO-dimethaxy-2-0x0-2H-

benzo[o]quinalizine- 3-corboxylote benzo[a]quinolizine-3-corboxamide (N)

H2 Roney -Ni

- _+

benzo[a]quinolizine-3-corboxornide (V)

acetic anhydride / Benquinornide

I

Rejierence(s):

US 3 053 845 (Pfizer; appl 29.8.1961)

US 3 055 894 (Pfizer; appl 9.3.1960)

BE 621 895 (Pfizer; appl 29.8.1962; USA-prior 9.3.1960,29.8.1961)

DE 1 303 628 (Pfizcr; appl 30.5.1962; USA-prior 29.8.1961.6.9.1961)

starting material:

Brossi, A eta].: Helv Chim Acta (HCACAV) 41, 119 (1958)

Trang 3

Benzthiazide B 213

Trade Name(s):

D: Promecon (Endopharm) Promecon (Searle) USA: Emete-Con (Roerig)

Benzthiazide

(Benzothiazide; Benztiazide)

ATC: C03 Use: diuretic, antihypertensive

RN: 91-33-8 MF: C,5H,4C1N304S3 MW: 431.95 EINECS: 202-061-0

LD,,: 410mg/kg(M, i.v.); >5 glkg (M, p.0.);

422 mglkg (R, i.v.); >10 glkg (R, p.0.);

>5 gtkg (dog, p.0.)

CN: 6-chloro-3-[[(phenylmethyl)thio]methyl]-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,l-dioxide

5-chloro-2.4-diomino- chloro- 7-ominonulfonyl-6-chloro-3-(chlo;omethyl)-

sulfonylaniline acetaldehyde 2H-1.2.4-benzothiadiozine 1.1-dioxide (I)

Formulation(s): cps 25 mg

benzyl

Trade Name(s):

D: Sali-Raufuncton (Minden)- Tensimic (Roussel); wfm Regulon (Yamanouchi) comb.; wfm GB: Dytide (Pharmark)-comb

F: Diteriam (Roussel)-comb with triamterene

with triamterene; wfm J: Fovane (Taito Pfizer)

Benzthiozide

Benzydamine

mercapton

ATC: AOlAD02; G02CC03; MOlAX07; M02AA05; M02AX

Use: analgesic, antipyretic, anti- inflammatory

RN: 642-72-8 MF: C,,H,,N,O MW: 309.41 EINECS: 211-388-8

LD,: 25 mg/kg (M, i.v.); 460 mglkg (M, p.0.);

950 mglkg (R, p.0.)

CN: N,N-dimethyl-3-[[l-(phenylmethyl)-1H-indazol-3-yl]oxy]-l-propanamine

monohydrochloride

RN: 132-69-4 MF: C,,H2,N3O HCl MW: 345.87 EINECS: 205-076-0

LD,,,: 33 mg/kg (M, i.v.); 440 mglkg (M, p.0.);

43.5 mg/kg (R, i.v.); 740 mglkg (R, p.0.)

Trang 4

2 1 4 B Benzyl alcohol

1 HCI NoN02 2.NoHS03

0

methyl benzyl

onthronilate chloride

1 NoOCH3

2 C I - N ~ ~ ~ ~

CH3

I

1 sodium methylote

2 3-dimethylomino-

propyl chloride

methyl 2-benzyl- ominobenzaote

Benzydomine

1 -benzyl-3-hydroxy-

1 H-indozole (I)

1 382 855 (Angelini Francesco; appl 21.2.1964; I-prior 9.8.1963)

Formulation(s): amp 25 mg; cps 50 mg; cream 30 mg; drg 50 mg; drops 50 mg; liquid 1.5 mg;

powder 500 mg (as hydrochloride)

Trade Narne(s):

D: Tantum (Solvay

Arzneimittel)

F: Opalgyne (Innothtra)

GB: Difflam (3M; as

hydrochloride)

I: Afloben (Esseti)

Berzirin (Fater)

Ginesal (Farmigea) J:

Leucorsan (Zil1iken)-comb

Multum (Lampugnani) Benzyrin (Yoshitomi)

Tantum Biotic (Ange1ini)- Epirotin (Nakataki) comb with tetracycline Lilizin (Beppu) Verax (Tosi-Novara) Riripen (Daiichi) numerous combination Salyzoron (Hishiyama)

Ant01 (Seiko Eiyo) Benzidan (Nikken)

(Alcoholum benzylicum; Phenylcarbinolum) Use: disinfectant, local anesthetic RN: 100-51-6 MF: C,H,O MW: 108.14 EINECS: 202-859-9

LD,,: 324 mglkg (M, i.v.j; 1360 mglkg (M, p.0.);

53 m g k g (R, i.v.); 1230 m g k g (R, p.0.)

CN: benzenemethanol

benzyl

chloride

Benzyl olcohol

L

Reference(s):

Ullmanns Encykl Tech Chem., 4 Aufl., Vol 8,437

Formulation(s): amp 1 %, 2 %; cream 1 %; sol 1 g1100 g

Trang 5

Benzyl benzoate B 2 15

Trade Name(s):

D: Spitacid (Henke1)-comb GB: Pabrinex (Link)-comb Foille (Delalande Isnardi) numerous combination Sudocrem (Tosara)-comb comb

preparations I: Borocaina (Schiapparelli)

Benzyl benzoate

(Benzoesaurebenzylester)

ATC: P03AXOl Use: scabicide, pharmaceutic agent RN: 120-51-4 MF: CI4Hl2O2 MW: 212.25 EINECS: 204-402-9

LD,,,: 1400 yUkg (M, p.0.);

1700 yL1kg (R, p.0.);

>22440 mglkg (dog, p.0.)

CN: benzoic acid phenylmethyl ester

benzooie chloride

I Benzyl benzooie I

Rejerence(s):

Tharp, I.D et al.: Ind Eng Chem (IECHAD) 39, 1300 (1947)

Formulation(s): emulsion 250 mg

Trade Name(s):

D: Acarosan (Allergopharma) Anusol HC (Warner- I: Antiscabbia Candioli a1 Antiscabiosum Mago KG Lambert)-comb D.D.T terap (Candio1i)-

Davis)-comb

Benzyl mustard oil

(Oleum tropaeoli)

ATC: SOlAA Use: antibiotic

RN: 622-78-6 MF: C,H,NS MW: 149.22 EINECS: 210-753-9

LD,,,: 150 mg/kg (M, s.c.)

CN: (isothiocyanatomethy1)benzene

bemylomine omrnonium N-benzylthioureo

hydrachloride rhodonide

Rejerence(s):

Ullmams Encykl Tech Chem., 4 Aufl., Vol 23, 156

Trang 6

216 B Benzylpenicillin

Trade Name(s):

D: Soledurn (Cassella-rned)-

comb

Benz ylpenicillin

(Penicillin G)

ATC: JOlCE01; JOlHA; SOlAA14 Use: antibiotic

RN: 61-33-6 MF: C,,H,,N2O4S MW: 334.40 EINECS: 200-506-3

LD,,: 329 mglkg (M, i.v.); >5 &/kg (M, p.0.);

8 glkg (R, p.0.)

CN: [2S-(2a,Sa,6~)]-3,3-dirnethyl-7-oxo-6-[(phenylacetyl)arnino]-4-thia-l-azabicyclo[3.2.0]heptane-2-

carboxylic acid

monosodium salt

RN: 69-57-8 MF: C,,H,,N,NaO,S MW 356.38 EINECS: 200-7 10-2

LD,,: 1500 rngkg (M, i.v.); >4 glkg (M, p.0.);

3020 m g k g (R, i.v.); 6916 rnglkg (R, p.0.)

monopotassium salt

RN: 113-98-4 MF: C,,H,,KN,04S MW: 372.49 EINECS: 204-038-0

LD,,: 240 rnglkg (M, i.v.); 6257 m g k g (M, p.0.);

243 mglkg (R, i.v.1; 8900 m g k g (R, p.0.)

COOH

Benzylpenicillin

From fermentation solutions of Penicillium notatum Westling or Penicillium chrysogenum Thorn by addition of

phenylacetic acid as precursor

Reference(s):

Ehrhart, Ruschig IV, 286 ff

Formulation(s): eft' tabl 653.6 rng; f c tabl 392.2 me, 653.6 rng, 982.32 rng; lyo for syrup 1986.59 mg Trade Name(s):

D: Megacillin (Griinentha1)-

comb

Penicillin Heyl (Heyl)

Prevecillin (Griinentha1)-

(clemizol-penicillin)

Tardocillin (Bayer)-

(benzathine-

benzylpenicillin)

F: Biclinocilline (Sanofi

Winthrop)-comb

Extencilline (Specia)-

(benzathine-

benzylpenicillin)

Penicilline G Diarnant (Roussel Diarnant) GB: Bicillin (Yamanouchi)- comb with procaine penicillin G Crystapen (Britannia) I: Benzil (Formulario Naz.) Penicillina Icar

(SrnithKline Beecham) Penicillina Sod Farm (Farrnitalia) Penicillina Squibb (Bristol- Myers Squibb)

J: Bicillin G (Wyeth-Banyo) USA: Bicillin (Wyeth-Ayerst) (benzathine-

benzylpenicillin) Pen (Wyeth-Ayerst)- (penicillin V potassium) Pfizerpen G (Pfizer)- (penicillin G potassium) Sugracillin (Upjohn) Wycillin (Wyeth-Ayerst) (procaine-benzylpenicillin)

Trang 7

Bephenium hydroxynaphthoate B 2 17

Use: anthelmintic RN: 3818-50-6 MF: C17H22N0 CllH703 MW: 443.54 EINECS: 223-306-8

CN: N,N-dimethyl-N-(2-phenoxyethyl)benzenemethanamium 3-hydroxy-2-naphthoate (1:l)

sodium 2-(dimethylomino)- N-(2-phenoxyethy1)-

phenolate ethyl chloride dimethylomine

Reference(s):

US 2 918 401 (Rorroughs Wellcome; 22.12.1959; GB-prior 29.3.1956)

DE 1 117 600 (Wellcome Found.; appl 21.3.1957; GB-prior 29.3.1956, ,24.1.1957)

bephenium chloride (I) sodium 3-hydmxy-

Formulation(s): gran 2.5 g, 4.33 g; powder 5 g

Bephenium hydroxynophthoote

Trade Namefs):

2 - n o ~ h t h o o t e

D: Alcopar (Wellcome); wfm J: Alcopar-P (Wellcome- USA: Alcopara (Borroughs

GB: Alcopar (Wellcome); wIm

Use: calcium channel blocker, antianginal RN: 64706-54-3 MF: C2,H3,N20 MW: 366.55 EINECS: 256-384-7

LD,: 1955 mgkg (M, p.0.); 23,s mgtkg (M, i.v.)

CN: a-[(2-methylpropoxy)methyl]-N-phenyl-N-(phenylmethyl)-l-pyrrolidineethanamine

monohydrochloride

RN: 68099-86-5 MF: C24H,4N20 HCl MW: 403.01 EINECS: 268-472-2

monohydrochloride monohydrate

RN: 74764-40-2 MF: C2,H,,N20 HCI H,O MW: 421.03

LDsn: 23.5 mglkg (M, i.v.); 1955 mg/kg (M, p.0.);

>21.3 mg/kg (R, i.v.); 6850 mg/kg (R, p.0.)

(+)-form

RN: 110143-74-3 MF: C2,H,,N20 MW: 366.55

(-)-form

RN: 110143-75-4 MF: C2,H3,N20 MW: 366.55

(*)-form

RN: 89035-90-5 MF: C2,H3,N,0 MW: 366.55

Trang 8

218 B Betacarotene

epichloro- isobutonol glycide isobutyl ether 1 -(2-hydroxy-3-iso-

SOCIZ CHCI3

I

thionyl

Reference(s):

DOS 2 3 10 918 (CERM; appl 5.3.1973; F-prior 6.3.1972)

DE 2 802 864 (CERM; ap& 13.1.1978; F-prior 25.1.1977)

US 3 962 238 (CERM; 8.6.1976; appl 27.2.1973; F-prior 6.3.1972)

GB 1 377 327 (CERM; appl 27.2.1973; F-prior 6.3.1972)

GB 1 595 031 (CERM; appl 13.1.1978; F-prior 25.1.1977)

Formulation(s): tabl 100 mg

Trade Narne(s):

F: Cordium (Riom; 1981) J: Bepricor (Nippon Organon; USA: Vascor (Ortho-McNeil; as

Sankyo; as hydrochloride hydrochloride) hydrate)

Betacarotene

@-Carotene; Betacarotin; p-Carotin)

ATC: D02BBO1 Use: provitamin A

RN: 7235-40-7 MF; C4&, MW: 536.89 EINECS: 230-636-6

CN: (all-E)-l,l'-(3,7,12,16-tetramethyl-l,3,5,7,9,11,13,15,17-octadecanonaene- 1,18-diyl)bis[2,6,6- trimethylcyclohexene]

1 Roche:

"oldehyde C,," triethyl

Trang 9

Betacarotene B 219

ethyl vinyl

ether

ethyl 1 -propenyl

ether

H,C CH CH CH, BrMg-C=C-MgBr

H 3 P 4 , dbxane H 2 0 wCHO (from H C r C H and C,Hs-UpBr)

-CH, acetylenebis(mognesium bromide)

Hz, Pd-Pb

H3 Lindlar catalyst 15-dehydro-@-carotene (VI)

80-100 "C in petraleum ether

15-cis-@-carotene (VII)

Trang 10

220 B Betacarotene

2 BASF:

retinol (VIII) triphenyl-

(4 v.) phosphine

CH, C H , ~ ~ ~ CH3

retinal

1.4-dibromo- trimethyl

2-butene phosphite

tetramethyl 2-butene-

1 -4-diylbisphosphonate

HsC-0

1 sodium methylate

2 rnethylglyoxal diethyl ocetol

OHC -HO + ydr, + F I

CH3 -

(all-E)-2.7-dirnethyl-2.4.6- triphenylphosphinylide

octotrienediol (XI) from vinyl-8-ionol

(cf retinol synthesis)

3 Rhone-Poulenc:

sodium retinyl phenyl sulfone (XII)

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